Pulmonary disease is a frequent manifestation of several types of the systemic connective tissue diseases (SCTD) such as rheumatoid arthritis, systemic lupus erythematosis, polymyositis, scleroderma, etc. The pathogenesis remains obscure, however. This proposal seeks to elucidate the pathogenic mechanisms of tissue injury in pulmonary $ manifestations of SCTD through a combined clinical and laboratory approach, utilizing methods of which some are already in use in the Vermont SCOR Program. We propose: (1) to investigate the effect of certain immune components (rheumatoid factor, antigen-antibody complexes, etc) associated with SCID on lung injury by means of their influence on human alveolar macrophage phagocytosis and lysosomal enzyme release and on fibrogenesis, as assayed by prolyl hydroxylase activity of bronchial lavage concentrates; (2) to investigate immune damage to lung tissue in animal models using light and electron microscopy, in addition to other techniques; (3) to evaluate hyperviscosity as a factor in the pulmonary disease; and (4) to correlate these mechanisms of tissue injury to clinical, radiographic, and physiologic function characteristics (including Xenon 133- scanning) of patients with SCTD and pulmonary manifestations, and to evaluate the effect of therapy on these mechanisms.